Induction of the hybrid B lymphocyte cell line TH 2.2 (BALB/c lymphoma X C57 B1 spleen cell) with LPS results in induction of growth in the line and secretion of IgM and of three cytokines, IL-3, IL-6, and GM-CSF. We have examined growth and cytokine secretion in clonal progeny of individual cells obtained by limiting dilution. Induced cells give rise to large (more 5000 cells/well) clones which can be recovered and grown indefinitely, and to microscopically visible (less 200 cells/well) clones which are terminal. The clonal frequency in the presence of LPS was less than 5% of the frequency among uninduced cells. Microscopic clones were most often highly specialized, secreting a single product, or at most two. The great majority of the clones making two products released IgM and one or another of the cytokines. This result suggests that the secretory products are produced by terminally differentiated cells with a narrow secretory specificity. The large clones varied greatly in size, over at least a tenfold range. Many clones were recovered which secreted only IgM; a few others secreted only single cytokines. Other clones were recovered which made various combinations of products, including a great many which made all four, and a few which secreted none. Clones of restricted and unrestricted secretory phenotype were recovered and retested. Those of restricted phenotype, including clones which had secreted none of the four products, could be induced by LPS to secrete all, or almost all of the products. Thus the phenotypic restriction is not the result of heritable genetic variation among the cells, but seems, rather, to be a reversible adaptive response to the conditions of culture and induction. The results show that a considerable diversity of response is rapidly generated among these cloned cells. In order to examine whether single cells make single or several products, and to determine if the diversity described above is generated in other cell lines, we have prepared riboprobes containing digoxigenin-labeled UTP (DIG-UTP) for use in studies employing in situ hybridization. The probes are detected with enzyme-labeled anti-DIG antibody by standard histochemical procedures.